Review Article Epoxyeicosatrienoic acids and soluble epoxide hydrolase: potential therapeutic targets for inflammation and its induced carcinogenesis
Stephanie Norwood, Jie Liao, Guang-Yu Yang
Department of Pathology, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Received June 15, 2010; accepted July 20, 2010; available online July 22, 2010
Abstract: Chronic inflammation is an important factor contributing to human carcinoma, and non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a preventive effect in the development of various types of carcinoma. However, NSAIDs also have adverse side effects including increased cardiovascular events, making them less than ideal for routine chemoprevention. Soluble epoxide hydrolase (sEH) is an enzyme that converts endogenous anti-inflammatory compounds, the epoxyeicosatrienoic acids (EETs), to the less anti-inflammatory dihydroxyeicosatrienoic acids (DHETs). Inhibition of sEH, by a highly selective and potent sEH inhibitor (sEHI), increases EETs leading to decreased inflammation. In our studies, administration of a sEHI in mouse colitis models led to decreased ulcer incidence and number of ulcers compared to controls, with no adverse side effects seen. In human tissue, sEH showed an increase in expression, as seen immunohistochemically, in ulcerative colitis (UC), UC-induced dysplasia, and UC-induced carcinoma. Thus, inhibition of sEH may be a novel biomarker and potential therapeutic target in inflammation and inflammation-induced carcinoma. (AJTR1006001).
Address all correspondence to: Guang-Yu Yang, M.D., Ph.D. Department of Pathology Northwestern University Feinberg School of Medicine 303 E. Chicago Avenue Chicago, Il 60611 Tel: 312-503-0645 Fax: 312-503-0647 E-mail: email@example.com